The purpose of this project is to utilize genomic data from many related organisms in order to learn more about functions of eukaryotic DNA, both coding noncoding. For coding sequences, we developed a method which uses rapid successions of single-nucleotide substitutions at the same codon as an indicator of positive selection, and identified many sites which evolved under such selection in rodent genomes. Also, we developed a method for in silico prediction of whether loss-of-function mutations at a particular gene would be morbid. For non-coding transcribed sequences, we analyzed patterns of evolutionary conservation in 3'UTRs and also developed an algorithm for finding regions of RNAs which are suitable for oligonucleotide targeting. We also continued work on comparative analysis of untranscribed intergenic regions. In particular, we developed an algorithm for calculating evolutionary distances on the basis of indels, instead of substitutions, and studied the dependence of indel mutation rates on their DNA context.